T cells are stimulated to respond via interaction of cell surface components with molecules present on the surface of antigen bearing cells. This cell-cell interaction involves the antigen specific T cell receptor and probably also involves interaction of 'accessory' molecules with ligands on the surface of the antigen bearing cell. Measurement of direct binding of antigen by T cells has, with a few exceptions, not been possible. It is possible, however, to measure functional binding of cytolytic T cells (CTL) to antigen-bearing target cells. Using this approach we found that CTL binding to target cells has the properties of an equilibrium binding process. Based on this observation, we were able to develop methods which allow quantitative measurement of the 'avidity' of this interaction and have shown that the avidity of T cell populations can vary depending on the conditions used for induction of the response. While this avidity measurement cannot be directly related to the affinity of the antigen specific receptor at the present time, it is in many respects a more meaningful measure, in that the functionally relevant effector unit is the intact T cell. Suggestions of avidity/affinity differences between CTL populations of clones have been invoked in attempts to explain many observed aspects of their effector function, but there has been little or no quantitative basis for such suggestions. Using the approaches we have developed, we will carry out systematic studies to examine the avidities of CTL cell populations (both allogeneic and antigen-specific CTL) and determine how the number and avidity of CTL is affected by antigen priming, stimulating antigen dose (and route), and levels of T cell help available during generation of the response. Based on the results of these studies, cloned CTL lines will be obtained and selected for further study based on determination that their avidities are representative of natural populations. Using these clones, we will examine the relative contributions of the antigen-specific receptor and accessory molecules to the avidity of the interaction. The results of the studies described in this proposal should lead to a much better understanding of the functional avidities of T cell populations and the parameters, both biological and molecular, which determine these avidities.